HPV-Related Squamous Cell Carcinoma Variants in the Head and Neck

The great majority of HPV-related carcinoma of the oropharynx is nonkeratinizing squamous cell carcinoma. More recently, an increasing number of squamous cell carcinoma variants that are HPV positive are being reported in the oropharynx, as well as in other head and neck sites. As a result, several clinical and pathologic questions have emerged. Importantly, questions raised include whether the virus is biologically active and involved in the pathogenesis of these tumors, and whether there are clinical implications with regard to patient outcome and treatment modality changes that may be needed in HPV-related variants. Examples of HPV-related squamous cell carcinoma variants that will be addressed here include: basaloid squamous cell carcinoma, undifferentiated carcinoma, adenosquamous carcinoma, papillary squamous carcinoma, and small cell carcinoma. Some investigations have suggested a favorable prognosis in some variants, analogous to that of the conventional nonkeratinizing (basaloid) carcinoma, while others showed poorer outcome. So far, the number of studies on this subject is limited and the number of cases evaluated in each investigation is few. Because of this, it is prudent at this stage not to alter management protocols as a result of identification of HPV in these variants and to await additional studies.